To assess mechanisms responsible for the clinical improvement observed in patients with hypertrophic cardiomyopathy while on verapamil therapy, we examined high temporal resolution time activity curves obtained from radionuclide cineangiography at rest in 45 patients before and after oral verapamil administration. Sixteen patients were also studied during oral propranolol therapy. Left ventricular systolic function was normal or supra-normal in all patients, but left ventricular diastolic filling was subnormal in 70 percent of patients. Systolic function was not altered during verapamil, but peak left ventricular filling rate significantly increased and time to peak filling rate significantly shortened. In contrast, propranolol did not alter diastolic events, but prolonged left ventricular ejection time and reduced ejection rate. Thus, verapamil improves abnormalities in left ventricular diastolic filling without altering systolic function. This mechanism may contribute to the clinical improvement of many patients with hypertrophic cardiomyopathy during verapamil therapy.